1. Field of the Invention
This invention relates generally to the field of medicine and, more specifically, to methods of inhibiting ectopic calcification.
2. Background Information
Deposition of calcium crystals in tissues other than teeth or bone, referred to as ectopic calcification, commonly occurs in association with renal failure, cardiovascular disease, diabetes and the aging process. A frequent finding in patients with renal failure, particularly those undergoing long-term hemodialysis and unable to appropriately regulate serum mineral balance, is calcification of internal organs, including the lung, heart, stomach and kidneys. Less commonly, hemodialysis patients develop painful calcified skin lesions that progress to non-healing ulcers or gangrene and may require amputation of the affected limb.
Ectopic calcification is also a common complication of the implantation of bioprosthetic heart valves and is the leading cause of replacement valve failure. Ectopic calcification also occurs in native heart valves and blood vessels in association with atherosclerosis, diabetes and cardiovascular disease. The deposition of minerals in the vasculature narrows the orifices and hardens the walls of the affected valves and blood vessels, resulting in reduced blood flow to the heart and peripheral organs. Therefore, ectopic calcification increases the risk of valve failure, stroke, ischemia and myocardial infarction.
One protein that is abundant at the sites of ectopic calcification, such as in atherosclerotic plaques and in calcified aortic valves, is osteopontin. Osteopontin has several known functions, including promoting cell adhesion, spreading and migration. Osteopontin colocalizes with sites of early calcification in coronary atherosclerotic plaques and its expression increases as atherosclerosis develops. These findings, combined with studies showing that osteopontin has calcium-binding properties in vitro, have led to the suggestion that osteopontin may be involved in ectopic calcification. Previous studies have not addressed the role of osteopontin in ectopic calcification in vivo.
Ectopic calcification, if left untreated, results in increased morbidity and death. Current therapies to normalize serum mineral levels or to inhibit calcification of vascular tissues or implants are of limited efficacy and cause unacceptable side effects.
Thus, there exists a need for an effective method of inhibiting ectopic calcification. The present invention satisfies this need and provides related advantages as well.
The invention provides a method of inhibiting ectopic calcification in an individual. The method consists of administering to the individual a therapeutically effective amount of osteopontin or a functional fragment thereof. The method can be used to inhibit ectopic calcification associated with a variety of conditions such as atherosclerosis, stenosis, restenosis, prosthetic valve replacement, angioplasty, renal failure, tissue injury, diabetes and aging.